Lithium t-Butoxy(t-butyl)cuprate1

t-BuCu(O-t-Bu)Li

[41655-91-8]  · C8H18CuLiO  · Lithium t-Butoxy(t-butyl)cuprate  · (MW 200.71)

(heterocuprate of greater thermal stability than analogous homocuprate;2 capable of nucleophilic additions2 and substitutions3)

Solubility: sol THF.

Analysis of Reagent Purity: an assay to determine relative thermal stabilities4 can be used to estimate reagent quality and concentration: a sample of known volume and temperature is quenched with excess PhCOCl; the yield of PhCO(t-Bu) is measured by GC, the response of which is calibrated using authentic product and n-dodecane as internal standard.

Preparative Methods: Lithium t-Butoxide is prepared2 under N2 by dropwise addition of 1.00 equiv of n-Butyllithium in hexanes to a solution of dry t-BuOH in dry THF3b (Potassium t-Butoxide should not be substituted for the lithium salt); a stirred suspension of 1.00 equiv of Copper(I) Iodide5 in dry THF at rt under N2 is treated with the t-BuOLi solution dropwise; after 15 min, the resulting cloudy, green-brown suspension is cooled to -78 °C and then treated with 1.00 equiv t-Butyllithium in pentane; the product, a cloudy, brown mixture, is ready for use after stirring for 5 min at -78 °C (alternative methods also may be acceptable; high-purity t-BuOLi is commercially available).6,7

Handling, Storage, and Precautions: best results are obtained with high-purity copper(I) salts,5,8 dry, oxygen-free solvents, and alkyllithium solutions free of contaminating alkoxides or hydroxides;9 the t-BuLi used to prepare the reagent is pyrophoric10 and due care must be exercised in its handling; use in a fume hood; thermal decomposition occurs at &egt;-30 °C, but the reagent is stable for one or more h at <=-50 °C.

Introduction.

The title reagent is representative of the heterocuprate class of organocopper reagents. The t-Bu group is reactive as a nucleophile, whereas the t-BuO group is not; such nontransferable groups are called dummy ligands.11 For t-Bu heterocuprates, t-BuO, PhO, and especially PhS dummy ligands are found to provide thermal stability compared to the parent homocuprate, (t-Bu)2CuLi.12 Heterocuprates generally exhibit less nucleophilic reactivity than corresponding homocuprates;13 however, increased thermal stabilities coupled with greater efficiency in use of the transferable ligand12 make them reasonable alternative reagents. This is particularly true when relatively high reaction temperatures are required, or when the organolithium used to form the cuprate is difficult or expensive to prepare.

Nucleophilic Substitutions of Halides.

The thermal stability of the cuprate typically results in higher chemical yields using highly reactive substrates such as Benzoyl Chloride (eq 1);12 in contrast, copper(I)-catalyzed reactions with t-BuLi or t-BuMgX are unsatisfactory. The low temperatures at which the reactions proceed allow for other, less reactive, functional groups to be present (eq 2).12

Reaction with a,a-dibromo ketones provides a regioselective, efficient route to a-tertiary and a-secondary alkylations of ketones (eq 3);5a,12,14 a-t-Bu alkylations using enolates or enolate equivalents generally are difficult and yields may be unsatisfactory. A related report indicates that the reagent is not effective when a-chlorophosphonates are used as substrates.15

The reagent has been used to effect simple SN2 reactions of iodoalkanes;12 it follows normal trends, providing good chemical yields for primary substrates only. Secondary exo-norbornenyl tosylates react to provide 2-t-butylnortricyclanes in good yield.16

1,4-Additions to 2-Alkenones.

While apparently not as effective as mixed homocuprates of general formula RC&tbond;CCu(t-Bu)Li, the reagent does act as a conjugate donor, undergoing slow 1,4-addition to 2-cyclohexenone (eq 4).11

Related Reagents.

See also Lithium Di-t-butylcuprate; for related heterocuprates, see, e.g. Lithium Methyl(phenylthio)cuprate; for discussion of lithium dialkylcuprates, see Lithium Dimethylcuprate.


1. (a) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (b) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980.
2. (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: New York, 1992. (b) Kozlowski, J. A. COS 1991, 4, 169. (c) Hulce, M.; Chapdelaine, M. J. COS 1991, 4, 237. (d) Chapdelaine, M. J.; Hulce, M. OR 1990, 38, 225. (e) Posner, G. H. OR 1975, 22, 253.
3. Posner, G. H. OR 1972, 19, 1.
4. Bertz, S. H.; Dabbagh, G. CC 1982, 1030.
5. Purification methods: (a) Posner, G. H.; Sterling, J. J. JACS 1973, 95, 3076. (b) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 322.
6. Huché, M.; Berlan, J.; Pourcelot, G.; Cresson, P. TL 1981, 22, 1329.
7. Mandeville, W. H.; Whitesides, G. M. JOC 1974, 39, 400.
8. Lipshutz, B. H.; Whitney, S.; Kozlowski, J. A.; Breneman, C. M. TL 1986, 27, 4273.
9. Corey, E. J.; Naef, R.; Hannon, F. J. JACS 1986, 108, 7114.
10. Wakefield, B. J. Organolithium Methods; Academic: New York, 1988; pp 11-15.
11. Lipshutz, B. H. SL 1990, 119.
12. Posner, G. H.; Whitten, C. E.; Sterling, J. J. JACS 1973, 95, 7788.
13. (a) Mandeville, W. H.; Whitesides, G. M. JOC 1974, 39, 400. (b) Whitesides, G. M.; Kendall, P. E. JOC 1972, 37, 3718.
14. Posner, G. H.; Sterling, J. J.; Whitten, C. E.; Lentz, C. M.; Brunelle, D. J. JACS 1975, 97, 107.
15. Villieras, J.; Reliquet, A.; Normant, J.-F. JOM 1978, 144, 17.
16. Posner, G. H.; Ting, J.-S.; Lentz, C. M. T 1976, 32, 2281.

Martin Hulce

Creighton University, Omaha, NE, USA



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